Mouse major histocompatibility complex (H-2) and fetal lung development: implications for human pulmonary maturation.
Using C57/10Sn (B10, H-2b) and B10.A/SgSn (B10.A,H-2a) congenic mice, we measured 1) the level of endogenous pulmonary corticosterone during mouse development; 2) the degree of lung morphological maturation on gestation day 17, with or without corticosteroid treatment; and 3) the maternal influence on normal lung development and fetal response to corticosteroids. The results of our study indicate that there was a progressive increase in the level of endogenous hormone with time in fetal B10 (H-2b) and B10.A (H-2a) mice; throughout mid- to late gestation, the detectable amount of hormone was almost identical in lungs of both strains. Evaluating the degree of lung maturation by morphometry, B10.A mouse lungs were found to be less mature than B10 mouse lungs. Following corticosteroid treatment on day 12 of gestation, H-2a lungs were equal to or more mature than H-2b lungs. We also compared heterozygous mouse lungs from reciprocal crosses (B10.B10.A, b/a and B10.A.B10, a/b). Mice with a maternally derived H-2a haplotype had less mature lungs than those with a maternally derived H-2b haplotype, suggesting a maternal effect. When exogenous hormone was administered, all heterozygous mouse lungs increased in maturity regardless of the origin of the H-2a haplotype. The treated a/b or b/a lungs were more mature than homozygous b/b and less mature than homozygous a/a lungs. We conclude that progressive lung maturation is associated with a gene(s) at or near the H-2 complex, as is the ability to respond to corticosteroids.
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Graduate Program in Craniofacial Biology, School of Dentistry, University of Southern California, Los Angeles 90089-0641.
Jaskoll
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Minkin
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Melnick
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D000305:Adrenal Cortex Hormones / Q000032:analysis / Q000494:pharmacology; D000818:Animals; D005260:Female; D005333:Fetus; D008168:Lung / Q000187:drug effects / Q000196:embryology*; D008285:Major Histocompatibility Complex; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D011247:Pregnancy
D000305:Adrenal Cortex Hormones